This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this project is to test the feasibility of TiO2 and derivative nanoparticles (Co-Fe-TiO2 and Co-Fe-Au-TiO2) nanoparticles and nanoparticle bio-organic molecule nanocomposites as diagnostic and/or therapeutic vehicles. Our previous experiments in cultured cells have shown that TiO2-DNA nanocomposites have unique and novel biochemical properties that would be very suitable for biomedical uses (Paunesku, et al.. Nature Materials (2003) 2 (5):343-346). We have since developed several new nanoparticles, and we investigated different ways to induce cellular uptake of such nanoparticles/nanocomposites (Figure 1). Therefore, we are now poised to test these different nano-constructs in vivo, in mice. Our overall goals can be organized in two aims: Aim 1) Testing different nanoparticle derivatives of TiO2 for in vivo stability and distribution Aim 2) Testing different nanoparticle coatings for in vivo stability and establishing their effects on in vivo distribution. At the BioCAT beamline we are investigating presence of titanium, cobalt, iron, gold and relevant "biological" elements: P, S, Ca, Zn using X-ray fluorescence in different mouse tissue sections with large surface area. We inject the nanocomposites directly into tumor tissue or intravenously or intraperitoneally. We subsequently isolate different tissues, freeze and cryosection them. We look for overlap of Ti signal with fluorescence signals of other elements present in nanoparticles and map their presence in different areas of tissue by comparing these signals with the signals produced by P, S, Zn and other elements "naturally" present in tissues.